Selective early loss of polypeptides in liver microsomes of CCl4-treated rats. Relationship to cytochrome P-450 content.

Treatment of rats with carbon tetrachloride (CCl4) resulted in early reproducible losses of either one or two specific polypeptides (depending on the inducing agent with which the animals had been treated) in the molecular weight range of the multiple forms of cytochrome P-450. The loss was correlated with a decrease in total cytochrome P-450 content in the microsome. The results of this study and those in the accompanying report indicate that CCl4 was metabolized by a specific form of cytochrome P-450 (52,000 daltons), which was rapidly destroyed in the process. The early loss of this peptide occurred simultaneously with the previously demonstrated production of highly reactive trichloromethyl radicals (CCl3). This polypeptide, which was shown to disappear from liver microsomes following treatment of rats with CCl4 was demonstrated in the accompanying report to be the form of cytochrome P-450 specifically required for production of the highly reactive trichloromethyl radical in a reconstituted monooxygenase system.